--- res: bibo_abstract: - "Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells, allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy, likely due to the cells’ heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E, R576Q, K493S, and K459S), resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette for use in combination with the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency.\r\n@eng" bibo_authorlist: - foaf_Person: foaf_givenName: Margaret E foaf_name: Maes, Margaret E foaf_surname: Maes foaf_workInfoHomepage: http://www.librecat.org/personId=3838F452-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0001-9642-1085 - foaf_Person: foaf_givenName: Gabriele M. foaf_name: Wögenstein, Gabriele M. foaf_surname: Wögenstein - foaf_Person: foaf_givenName: Gloria foaf_name: Colombo, Gloria foaf_surname: Colombo foaf_workInfoHomepage: http://www.librecat.org/personId=3483CF6C-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0001-9434-8902 - foaf_Person: foaf_givenName: Raquel foaf_name: Casado Polanco, Raquel foaf_surname: Casado Polanco foaf_workInfoHomepage: http://www.librecat.org/personId=15240fc1-dbcd-11ea-9d1d-ac5a786425fd orcid: 0000-0001-8293-4568 - foaf_Person: foaf_givenName: Sandra foaf_name: Siegert, Sandra foaf_surname: Siegert foaf_workInfoHomepage: http://www.librecat.org/personId=36ACD32E-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0001-8635-0877 bibo_doi: 10.1016/j.omtm.2021.09.006 bibo_volume: 23 dct_date: 2021^xs_gYear dct_identifier: - UT:000748748500019 dct_isPartOf: - http://id.crossref.org/issn/2329-0501 dct_language: eng dct_publisher: Elsevier@ dct_title: Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment@ ...